As Beej pointed out (along with other good info), experiment.
After years of having a fairly involved rack of FX, I find that adjusting the send levels on FX and on the loop of the amp to be a very involved process. If I get my amp set up just right so that it is very responsive, inserting a processor in the loop really makes it much more difficult to keep the same balance of preamp gain vs. power amp gain. Add to this, the fact that it is necessary to adjust carefully to preserve a good signal-noise ratio makes things even more tricky.
As a result of wanting to keep things simple, I went back to using pedals (almost exclusively). Even though flange, chorus, delay, reverb, etc. are commonly placed in the loop, I find that if you are using pedals for these effects (instead of rackmount processors) they sound best in front of the amp even though many will work fine in the loop.
Some of the best chorus sounds of all time were done with a pedal into the front end of an amp. Stompbox FX, many times, have more character than their high end, rackmount counterparts. Similarly, Univibes, flangers, and phasers tend to sound better in front of an amp than in the loop. That is not to say they won't work in the loop of course.
Delay usually sounds best AFTER distortion. So, if you get your gain sounds from the amp, you will likely need to put the delay in the loop. In my case, I have a stompbox delay on my pedalboard before the amp, as well as a rackmount delay that is the only thing in the loop of my amp. The stompbox delay sounds great with clean tones, and also can be used when I get overdrive from a pedal on the pedalboard. I use the amp for high-gain tones, and therefore have to use the rackmount delay for those sounds.
When using a loop, it is usually necessary to add some type of switcher and/or line mixer in a loop because, with most FX processors, your unaffected tone is still going through lots of extra circuitry and maybe even A/D - D/A convertors - even when the effect is bypassed! If your amp has a parallel FX loop and can be bypassed you don't need to add the switcher or mixer (unless you have more than one effect in the loop and want contol over each unit).
Here are a few things to consider.
1. Search for the most transparent FX processors you can find if you plan on putting them in the amp's effect loop. Remember that you may need to add a switcher and/or line mixer if you really want to add FX without compromising your basic tone in any way.
2. If you want a particular effect, try to find a pedal that will do the job. They usually have more character. And, although anything placed in your signal path will affect the tone, pedals in my opinion do it in a musical way, as opposed to the harsh, non-musical, feel-destroying effect that some rackmount processors have on your tone.
3. The above suggestion is subjective of course. If you are going for a very pristine sound, then many times, rackmount processors are the way to go.
4. Even though stompboxes sound cool, it is always a good idea to be able to bypass them so that you can get the pure sound of guitar into amp when you want it. Using a simple box with a single bypass loop allows you to bypass all your pedals with one stomp. This can be a lifesaver if, on a gig, one pedal goes bad as you can easily switch the whole string of pedals out of your signal path and keep playing.
5. If you are debating using a multi-FX unit for all of your FX, these probably sound best in the loop. Unless it is the floor type, which often incorporate stompbox style FX and digital FX processing in one unit. If you are only using the delays and reverbs, a unit like this may sound best in the loop of your amp.
Placing your FX in the loop vs. the front end of the amp really depends on what FX you are using, and where your distortion tones come from.
I hope this info is helpful (sorry for the long post!).
Terry
